Interrelationship of dipeptidyl peptidase IV (DPP4) with the development of diabetes, dyslipidaemia and nephropathy: a streptozotocin-induced model using wild-type and DPP4-deficient rats.
We examined the role of dipeptidyl peptidase IV (DPP4) in the development of diabetes, dyslipidaemia and renal dysfunction induced by streptozotocin (STZ). F344/DuCrlCrlj rats, which lack DPP4 activity, and wild-type rats were treated with STZ. Plasma DPP4 activity and biochemical parameters were measured until 42 days after STZ treatment. At the end of the experiment, renal function and DPP4 expressions of the kidney, liver, pancreas and adipose tissues were determined. Increases in blood glucose, cholesterol and triglycerides were evoked by STZ in both rat strains; however, the onset of hyperglycaemia was delayed in DPP4-deficient rats as compared with wild-type rats. By contrast, more severe dyslipidaemia was observed in DPP4-deficient rats than in wild-type rats after STZ treatment. Plasma DPP4 activity increased progressively with time after STZ treatment in wild-type rats. The kidney of wild-type rats showed decreased DPP4 activity with increased Dpp4 mRNA after STZ treatment. In addition, kidney weight, serum creatinine and excreted amounts of urinary protein, glucose and DPP4 enzyme were enhanced by STZ. DPP4-deficient rats showed increased serum creatinine in accordance with decreased creatinine clearance as compared with wild-type rats after STZ treatment. In conclusion, plasma DPP4 activity increased after STZ treatment, positively correlating to blood glucose. DPP4-deficient rats were resistant to developing diabetes, while susceptible to dyslipidaemia and reduction of glomerular filtration rate by STZ. DPP4 activation may be responsible for hyperglycaemia, lipid metabolism and preservation of renal function.
Kirino
Yasushi
Y
Department of Human Genetics and Public Health, Institute of Health Biosciences, The University of Tokushima Graduate School, The University of Tokushima, Kuramoto-Cho, Tokushima, Japan.
Sato
Youichi
Y
Kamimoto
Takayuki
T
Kawazoe
Kazuyoshi
K
Minakuchi
Kazuo
K
Nakahori
Yutaka
Y
D000818:Animals; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018819:Dipeptidyl Peptidase 4 / Q000097:blood / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D050171:Dyslipidemias / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008297:Male; D051381:Rats; D055647:Rats, Transgenic; D013311:Streptozocin
D013311:Streptozocin; D002784:Cholesterol; D003404:Creatinine; D018819:Dipeptidyl Peptidase 4